Human umbilical cord blood is a rich source of hematopoietic stem cells that can be used to re-populate the blood and immune systems. In preliminary studies we have identified a novel population of non-hematopoietic cells that exhibit extensive self-renewal and markers characteristic of stem cells. We postulate that these cells can be used to repair the brain following ischemic injury. In specific aim 1 we will conduct studies to compare high vs. low passage stem cells to determine whether high passage cells can repair the brain and restore function in a rodent model of experimental stroke. In specific aim 2 we will conduct cell dose-response experiments to determine an optimal range in the number of stem cells that minimizes neurological and neuropathological deficits. Behavioral tests and novel magnetic resonance protocols will be used to assess neurological function. In specific aim 3, the ability of the transplanted cells to differentiate into neural cells will be assessed by immunohistochemistry. The ability of the grafted cells to induce neurogenesis and vascular neogenesis will also be assessed. The results from this study will provide information on whether non- hematopoietic cord blood stem cells can be used as a therapy for treating ischemic brain injury. PUBLIC HEALTH RELEVANCE: Stroke resulting from ischemic brain injury is a major cause of disability and death in this country. At the present time drugs that are used to treat ischemic stroke must be administered within 3 hours after the ischemic event in order to be effective. We have discovered a unique population of umbilical cord stem cells that appear to reduce the size of lesions in the brain that result from experimental ischemia and minimize the extent of neurological deficits even when administered 48 hours after the stroke. Our proposed project intends to determine whether these cells can be developed as a therapy for treating patients who have suffered ischemic injuries to the brain. [unreadable] [unreadable] [unreadable]